TW200536541A - Substituted methyl aryl or heteroaryl amide compounds - Google Patents
Substituted methyl aryl or heteroaryl amide compounds Download PDFInfo
- Publication number
- TW200536541A TW200536541A TW094114245A TW94114245A TW200536541A TW 200536541 A TW200536541 A TW 200536541A TW 094114245 A TW094114245 A TW 094114245A TW 94114245 A TW94114245 A TW 94114245A TW 200536541 A TW200536541 A TW 200536541A
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- TW
- Taiwan
- Prior art keywords
- group
- carbon atoms
- ethyl
- methyl
- amino
- Prior art date
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- -1 heteroaryl amide compounds Chemical class 0.000 title claims abstract description 237
- 150000001875 compounds Chemical class 0.000 claims abstract description 283
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 71
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 37
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 12
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 8
- 150000003180 prostaglandins Chemical class 0.000 claims abstract description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 136
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 117
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 91
- 239000000203 mixture Substances 0.000 claims description 88
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 73
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 59
- 239000005711 Benzoic acid Substances 0.000 claims description 56
- 235000010233 benzoic acid Nutrition 0.000 claims description 56
- 150000003839 salts Chemical class 0.000 claims description 41
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 38
- 239000003814 drug Substances 0.000 claims description 23
- 125000001424 substituent group Chemical group 0.000 claims description 21
- 229940079593 drug Drugs 0.000 claims description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
- 229910052757 nitrogen Inorganic materials 0.000 claims description 16
- 125000003545 alkoxy group Chemical group 0.000 claims description 15
- WAJUCMNAGKFHLB-UHFFFAOYSA-N phenylarsinic acid Chemical compound O[AsH](=O)C1=CC=CC=C1 WAJUCMNAGKFHLB-UHFFFAOYSA-N 0.000 claims description 14
- 125000004429 atom Chemical group 0.000 claims description 13
- 150000002148 esters Chemical class 0.000 claims description 13
- 239000001301 oxygen Substances 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- 125000005843 halogen group Chemical group 0.000 claims description 11
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 10
- 229910052801 chlorine Inorganic materials 0.000 claims description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
- 229910052731 fluorine Inorganic materials 0.000 claims description 7
- 125000000623 heterocyclic group Chemical group 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- 125000001153 fluoro group Chemical group F* 0.000 claims description 5
- 125000001188 haloalkyl group Chemical group 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- 239000000052 vinegar Substances 0.000 claims description 5
- 235000021419 vinegar Nutrition 0.000 claims description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- UKXSKSHDVLQNKG-UHFFFAOYSA-N benzilic acid Chemical compound C=1C=CC=CC=1C(O)(C(=O)O)C1=CC=CC=C1 UKXSKSHDVLQNKG-UHFFFAOYSA-N 0.000 claims description 4
- 238000001727 in vivo Methods 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 230000001105 regulatory effect Effects 0.000 claims description 4
- 125000006413 ring segment Chemical group 0.000 claims description 4
- 239000002689 soil Substances 0.000 claims description 4
- 241000124008 Mammalia Species 0.000 claims description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
- 238000006467 substitution reaction Methods 0.000 claims description 3
- 239000011593 sulfur Substances 0.000 claims description 3
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 2
- 238000010304 firing Methods 0.000 claims description 2
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 2
- 125000005842 heteroatom Chemical group 0.000 claims description 2
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 2
- 229940094443 oxytocics prostaglandins Drugs 0.000 claims description 2
- 239000004575 stone Substances 0.000 claims description 2
- 125000004434 sulfur atom Chemical group 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims 2
- ZSOUMKQBWCUSBE-UHFFFAOYSA-N C1(=CC=CC=C1)C1=C(C=2CC3=CC=CC=C3C2C=C1)C(=O)O Chemical compound C1(=CC=CC=C1)C1=C(C=2CC3=CC=CC=C3C2C=C1)C(=O)O ZSOUMKQBWCUSBE-UHFFFAOYSA-N 0.000 claims 1
- 239000013543 active substance Substances 0.000 claims 1
- 125000005257 alkyl acyl group Chemical group 0.000 claims 1
- 125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims 1
- 125000005630 sialyl group Chemical group 0.000 claims 1
- 208000002193 Pain Diseases 0.000 abstract description 62
- 230000036407 pain Effects 0.000 abstract description 56
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 35
- 201000010099 disease Diseases 0.000 abstract description 29
- 238000011282 treatment Methods 0.000 abstract description 10
- 125000001841 imino group Chemical group [H]N=* 0.000 abstract 1
- 230000001404 mediated effect Effects 0.000 abstract 1
- 238000000034 method Methods 0.000 description 132
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 73
- 239000002253 acid Substances 0.000 description 66
- 229960004365 benzoic acid Drugs 0.000 description 49
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- 238000012360 testing method Methods 0.000 description 44
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 43
- 238000006243 chemical reaction Methods 0.000 description 41
- 239000000243 solution Substances 0.000 description 41
- 210000004027 cell Anatomy 0.000 description 39
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 36
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 35
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 34
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 32
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 29
- 238000009472 formulation Methods 0.000 description 29
- 238000005481 NMR spectroscopy Methods 0.000 description 28
- 150000001412 amines Chemical class 0.000 description 28
- 239000002585 base Substances 0.000 description 27
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 26
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 26
- 235000019439 ethyl acetate Nutrition 0.000 description 25
- 239000007789 gas Substances 0.000 description 25
- 238000005160 1H NMR spectroscopy Methods 0.000 description 24
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 23
- 239000002904 solvent Substances 0.000 description 22
- 208000024891 symptom Diseases 0.000 description 22
- 235000019441 ethanol Nutrition 0.000 description 21
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 20
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 20
- 239000011541 reaction mixture Substances 0.000 description 20
- 229940050390 benzoate Drugs 0.000 description 19
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 239000000499 gel Substances 0.000 description 17
- WSFSSNUMVMOOMR-UHFFFAOYSA-N formaldehyde Natural products O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 16
- 230000006378 damage Effects 0.000 description 15
- 229910052739 hydrogen Inorganic materials 0.000 description 15
- 239000012442 inert solvent Substances 0.000 description 15
- 238000002360 preparation method Methods 0.000 description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 14
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 14
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 14
- 239000003795 chemical substances by application Substances 0.000 description 14
- 239000001257 hydrogen Substances 0.000 description 14
- 229910052938 sodium sulfate Inorganic materials 0.000 description 14
- 235000011152 sodium sulphate Nutrition 0.000 description 14
- 208000014674 injury Diseases 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- 235000011054 acetic acid Nutrition 0.000 description 12
- 229960000583 acetic acid Drugs 0.000 description 12
- 238000002347 injection Methods 0.000 description 12
- 239000007924 injection Substances 0.000 description 12
- 102000005962 receptors Human genes 0.000 description 12
- 108020003175 receptors Proteins 0.000 description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 11
- 241000700159 Rattus Species 0.000 description 11
- 239000003153 chemical reaction reagent Substances 0.000 description 11
- 239000007937 lozenge Substances 0.000 description 11
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 11
- 239000000843 powder Substances 0.000 description 11
- 239000007787 solid Substances 0.000 description 11
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 10
- 125000003118 aryl group Chemical group 0.000 description 10
- 230000027455 binding Effects 0.000 description 10
- 239000000872 buffer Substances 0.000 description 10
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 10
- 238000003818 flash chromatography Methods 0.000 description 10
- 229940002612 prodrug Drugs 0.000 description 10
- 239000000651 prodrug Substances 0.000 description 10
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 9
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- 239000002552 dosage form Substances 0.000 description 9
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- 208000004296 neuralgia Diseases 0.000 description 9
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
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- 238000002474 experimental method Methods 0.000 description 8
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- 235000010981 methylcellulose Nutrition 0.000 description 8
- 108090000623 proteins and genes Proteins 0.000 description 8
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 7
- 208000004454 Hyperalgesia Diseases 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 7
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- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 7
- 239000005557 antagonist Substances 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
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- 125000005998 bromoethyl group Chemical group 0.000 description 7
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- 229940095102 methyl benzoate Drugs 0.000 description 7
- MZDGXTXYHXDWIM-UHFFFAOYSA-N methyl benzoate;hydrochloride Chemical compound Cl.COC(=O)C1=CC=CC=C1 MZDGXTXYHXDWIM-UHFFFAOYSA-N 0.000 description 7
- 229920000609 methyl cellulose Polymers 0.000 description 7
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- 239000011734 sodium Substances 0.000 description 7
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
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Classifications
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- C07C235/42—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/44—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C235/46—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/65—One oxygen atom attached in position 3 or 5
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
- C07D213/82—Amides; Imides in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/89—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members with hetero atoms directly attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
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- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
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- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
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- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
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- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Pulmonology (AREA)
- Diabetes (AREA)
- Oncology (AREA)
- Rheumatology (AREA)
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- Transplantation (AREA)
- Endocrinology (AREA)
- Hospice & Palliative Care (AREA)
- Emergency Medicine (AREA)
- Obesity (AREA)
- Psychiatry (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pyridine Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (1)
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| US56808804P | 2004-05-04 | 2004-05-04 |
Publications (1)
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Country Status (29)
| Country | Link |
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| EP (1) | EP1756042B8 (fr) |
| JP (1) | JP4054368B2 (fr) |
| KR (1) | KR20070006891A (fr) |
| CN (1) | CN1950333A (fr) |
| AP (1) | AP2006003785A0 (fr) |
| AR (1) | AR048642A1 (fr) |
| AU (1) | AU2005238291A1 (fr) |
| BR (1) | BRPI0510666A (fr) |
| CA (1) | CA2565813C (fr) |
| CR (1) | CR8730A (fr) |
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| EA (1) | EA200601847A1 (fr) |
| EC (1) | ECSP066968A (fr) |
| ES (1) | ES2461265T3 (fr) |
| GT (1) | GT200500101A (fr) |
| IL (1) | IL178676A0 (fr) |
| MA (1) | MA28571B1 (fr) |
| MX (1) | MXPA06011555A (fr) |
| NL (1) | NL1028947C2 (fr) |
| NO (1) | NO20065578L (fr) |
| PA (1) | PA8631201A1 (fr) |
| PE (1) | PE20060306A1 (fr) |
| SV (1) | SV2005002102A (fr) |
| TN (1) | TNSN06358A1 (fr) |
| TW (1) | TW200536541A (fr) |
| UY (1) | UY28877A1 (fr) |
| WO (1) | WO2005105732A1 (fr) |
| ZA (1) | ZA200608393B (fr) |
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| ES2398579T3 (es) * | 2005-09-19 | 2013-03-20 | Teva Pharmaceutical Industries Ltd | Una síntesis asimétrica de ácido (S)-(+)-3-(aminometil)-5-metilhexanoico |
| DE102005062966A1 (de) * | 2005-12-28 | 2007-07-05 | Basf Ag | Verfahren zur Herstellung von (R)- und (S)-4-(Ammoniumethyl)benzoesäuremethylester-sulfat |
| JP5329973B2 (ja) * | 2005-12-28 | 2013-10-30 | ビーエーエスエフ ソシエタス・ヨーロピア | リパーゼ触媒を用いるエナンチオ選択的アシル化とその後の硫酸による沈殿によって、ラセミ体の4−(1−アミノエチル)安息香酸メチルエステルから(r)−および(s)−4−(1−アンモニウムエチル)安息香酸メチルエステル硫酸塩を調製する方法 |
| UY30121A1 (es) | 2006-02-03 | 2007-08-31 | Glaxo Group Ltd | Nuevos compuestos |
| US8969394B2 (en) | 2006-08-11 | 2015-03-03 | Merck Frosst Canada Ltd. | Thiophenecarboxamide derivatives as EP4 receptor ligands |
| AU2007331471C1 (en) | 2006-12-15 | 2013-07-25 | Glaxo Group Limited | Benzamide derivatives as EP4 receptor agonists |
| JP5408434B2 (ja) * | 2007-07-03 | 2014-02-05 | アステラス製薬株式会社 | アミド化合物 |
| GB0721611D0 (en) * | 2007-11-02 | 2007-12-12 | Glaxo Group Ltd | Novel compounds |
| EP2565191B1 (fr) * | 2008-05-14 | 2014-10-08 | Astellas Pharma Inc. | Dérivés d'acide 4-(indol-7-ylcarbonylaminométhyl)cyclohexanecarboxylique comme antagonistes du récepteur EP4 utilisables pour le traitement de l'insuffisance rénale chronique ou de la néphropathie diabétique |
| EP2297090A1 (fr) * | 2008-06-23 | 2011-03-23 | Teva Pharmaceutical Industries Ltd. | Synthèse enzymatique stéréosélective de l ester (s) ou (r)-isobutylglutarique |
| EP2392323A4 (fr) | 2009-01-30 | 2012-09-26 | Univ Kyoto | Inhibiteur de la progression du cancer de la prostate et procédé d'inhibition de la progression |
| EP2965756B1 (fr) | 2009-04-22 | 2018-10-10 | AskAt Inc. | Substance antagoniste sélective du récepteur ep4 pour le traitement du cancer |
| US9457084B2 (en) * | 2010-02-22 | 2016-10-04 | Raqualia Pharma Inc. | Use of EP4 receptor antagonists in the treatment of IL-23 mediated diseases |
| PE20131343A1 (es) | 2010-09-21 | 2013-11-18 | Eisai Randd Man Co Ltd | Derivados de acido benzoico |
| WO2012076063A1 (fr) | 2010-12-10 | 2012-06-14 | Rottapharm S.P.A. | Dérivés de pyridinamide en tant qu'antagonistes de récepteur ep4 |
| DK2729445T3 (en) | 2011-07-04 | 2016-01-18 | Rottapharm Biotech Srl | CYCLIC AMINE DERIVATIVES AS EP4 RECEPTOR ANTAGONISTS |
| US9096794B2 (en) | 2011-08-29 | 2015-08-04 | Ticona Llc | High flow liquid crystalline polymer composition |
| JP2014525499A (ja) | 2011-08-29 | 2014-09-29 | ティコナ・エルエルシー | 低い融解温度をもつ耐熱性液晶ポリマー組成物 |
| WO2013032973A1 (fr) | 2011-08-29 | 2013-03-07 | Ticona Llc | Composé de type amide aromatique |
| WO2013032971A1 (fr) | 2011-08-29 | 2013-03-07 | Ticona Llc | Substrat extrudé à l'état fondu destiné être utilisé dans des articles thermoformés |
| US9074133B2 (en) | 2011-08-29 | 2015-07-07 | Ticona Llc | Thermotropic liquid crystalline polymer with improved low shear viscosity |
| CN103764793B (zh) | 2011-08-29 | 2016-09-14 | 提克纳有限责任公司 | 高流动液晶聚合物组合物 |
| JP2014525500A (ja) | 2011-08-29 | 2014-09-29 | ティコナ・エルエルシー | 低溶融粘度液晶ポリマーの溶融重合 |
| TW201313884A (zh) | 2011-08-29 | 2013-04-01 | Ticona Llc | 液晶聚合物之固態聚合 |
| WO2013032967A1 (fr) | 2011-08-29 | 2013-03-07 | Ticona Llc | Pièces coulées au moule formées à partir d'un polymère cristallin liquide |
| JO3296B1 (ar) | 2012-06-29 | 2018-09-16 | Lilly Co Eli | مركبات فينوكسي إيثيل بيبريدين |
| US9757395B2 (en) | 2012-12-20 | 2017-09-12 | Otitopic Inc. | Dry powder inhaler and methods of use |
| US9757529B2 (en) | 2012-12-20 | 2017-09-12 | Otitopic Inc. | Dry powder inhaler and methods of use |
| WO2014130275A2 (fr) | 2013-02-22 | 2014-08-28 | Ticona Llc | Composition de polymères haute performance présentant des propriétés d'écoulement améliorées |
| CA2907049C (fr) | 2013-03-19 | 2021-08-10 | Askat Inc. | Utilisation d'antagonistes de recepteur ep4 dans le traitement d'une maladie du cartilage |
| US10391086B2 (en) | 2013-03-19 | 2019-08-27 | Askat Inc. | Use of EP4 receptor antagonists in the treatment of cartilage disease |
| AU2013388034B2 (en) | 2013-04-30 | 2019-08-15 | Aspeya US Inc. | Dry powder formulations and methods of use |
| TWI636046B (zh) | 2013-05-17 | 2018-09-21 | 美國禮來大藥廠 | 苯氧基乙基二氫-1h-異喹啉化合物 |
| JP6625050B2 (ja) | 2013-06-07 | 2019-12-25 | ティコナ・エルエルシー | 高強度サーモトロピック液晶ポリマー |
| CA2914997C (fr) | 2013-06-12 | 2021-07-20 | Kaken Pharmaceutical Co., Ltd. | Derive de 4-alcynylimidazole et medicament le comprenant en tant que principe actif |
| ME02896B (fr) | 2013-12-17 | 2018-04-20 | Lilly Co Eli | Dérivés d'amine cyclique de phénoxyéthyle et leur activité en tant que modulateurs du récepteur ep4 |
| CR20180323A (es) | 2015-11-20 | 2018-08-06 | Idorsia Pharmaceuticals Ltd | Derivados de indol n-sustituídos como moduladores de los receptores de pge2 |
| US10342785B2 (en) | 2016-11-04 | 2019-07-09 | Askat Inc. | Use of EP4 receptor antagonists for the treatment of NASH-associated liver cancer |
| TWI768043B (zh) | 2017-05-18 | 2022-06-21 | 瑞士商愛杜西亞製藥有限公司 | N-取代吲哚衍生物 |
| US11839613B2 (en) | 2017-05-18 | 2023-12-12 | Idorsia Pharmaceuticals Ltd | Pyrimidine derivatives as PGE2 receptor modulators |
| KR102612140B1 (ko) | 2017-05-18 | 2023-12-08 | 이도르시아 파마슈티컬스 리미티드 | 피리미딘 유도체 |
| PE20191814A1 (es) | 2017-05-18 | 2019-12-27 | Idorsia Pharmaceuticals Ltd | Derivados de pirimidina como moduladores del receptor de pge2 |
| TW201900179A (zh) | 2017-05-18 | 2019-01-01 | 瑞士商愛杜西亞製藥有限公司 | 作為pge2受體調節劑之苯并呋喃及苯并噻吩衍生物 |
| SK592017A3 (sk) * | 2017-07-04 | 2019-01-08 | Saneca Pharmaceuticals A. S. | Spôsob prípravy morfínanových zlúčenín |
| JP7493449B2 (ja) | 2017-09-22 | 2024-05-31 | ヴェクチュラ インコーポレイテッド | ステアリン酸マグネシウムを含む乾燥粉末組成物 |
| US10786456B2 (en) | 2017-09-22 | 2020-09-29 | Otitopic Inc. | Inhaled aspirin and magnesium to treat inflammation |
| CN114555573B (zh) * | 2019-10-02 | 2025-08-15 | 多曼治疗学公司 | 前列腺素e2(pge2)ep4受体拮抗剂 |
| CN114075140A (zh) * | 2020-08-18 | 2022-02-22 | 武汉人福创新药物研发中心有限公司 | 作为ep4受体拮抗剂的吡唑酰胺衍生物及其在癌症和炎症中的用途 |
| US20230390303A1 (en) | 2020-11-13 | 2023-12-07 | Ono Pharmaceutical Co., Ltd. | Cancer treatment by combination of ep4 antagonist and immune checkpoint inhibitor |
| CN114790176A (zh) * | 2021-01-25 | 2022-07-26 | 武汉人福创新药物研发中心有限公司 | 咪唑类化合物及其制备方法和用途 |
| GB202211232D0 (en) | 2022-08-02 | 2022-09-14 | Heptares Therapeutics Ltd | Prostaglandin EP4 receptor agonist compounds |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19648793A1 (de) | 1996-11-26 | 1998-05-28 | Basf Ag | Neue Benzamide und deren Anwendung |
| TW523506B (en) * | 1996-12-18 | 2003-03-11 | Ono Pharmaceutical Co | Sulfonamide or carbamide derivatives and drugs containing the same as active ingredients |
| AU738037B2 (en) | 1997-04-04 | 2001-09-06 | Pfizer Products Inc. | Nicotinamide derivatives |
| US6211197B1 (en) * | 1998-10-07 | 2001-04-03 | Merck Frosst Canada & Co. | Prostaglandin receptor ligands |
| CA2374947A1 (fr) | 1999-05-24 | 2000-11-30 | Robert M. Scarborough | Inhibiteurs du facteur xa |
| US6924391B2 (en) * | 2000-05-11 | 2005-08-02 | Bristol-Myers Squibb Company | Alpha-amino,-thio,-oxo substituted ketones as phospholipase inhibitors |
| DE60203652T2 (de) | 2001-01-31 | 2005-09-08 | Pfizer Products Inc., Groton | Nikotinsäureamid-Derivate und ihre Mimetika als Inhibitoren von PDE4-Isozyme |
| CN101284773A (zh) | 2001-08-09 | 2008-10-15 | 小野药品工业株式会社 | 羧酸衍生物及以它为活性成分的药剂 |
| WO2003030937A1 (fr) | 2001-10-05 | 2003-04-17 | Ono Pharmaceutical Co., Ltd. | Remedes contre des maladies liees au stress comprenant des antagonistes de recepteurs mithochondriaux de la benzodiazepine |
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2005
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- 2005-04-22 AP AP2006003785A patent/AP2006003785A0/xx unknown
- 2005-04-22 BR BRPI0510666-4A patent/BRPI0510666A/pt not_active IP Right Cessation
- 2005-04-22 WO PCT/IB2005/001134 patent/WO2005105732A1/fr not_active Ceased
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- 2005-04-22 KR KR1020067023128A patent/KR20070006891A/ko not_active Abandoned
- 2005-04-22 EP EP05733780.0A patent/EP1756042B8/fr not_active Expired - Lifetime
- 2005-04-22 CA CA2565813A patent/CA2565813C/fr not_active Expired - Lifetime
- 2005-04-22 EA EA200601847A patent/EA200601847A1/ru unknown
- 2005-04-22 AU AU2005238291A patent/AU2005238291A1/en not_active Abandoned
- 2005-04-22 CN CNA2005800141028A patent/CN1950333A/zh active Pending
- 2005-04-22 JP JP2007512542A patent/JP4054368B2/ja not_active Expired - Lifetime
- 2005-04-27 PA PA20058631201A patent/PA8631201A1/es unknown
- 2005-04-29 DO DO2005000071A patent/DOP2005000071A/es unknown
- 2005-04-29 UY UY28877A patent/UY28877A1/es not_active Application Discontinuation
- 2005-04-29 US US11/118,497 patent/US7534914B2/en not_active Expired - Fee Related
- 2005-05-02 AR ARP050101745A patent/AR048642A1/es unknown
- 2005-05-03 NL NL1028947A patent/NL1028947C2/nl not_active IP Right Cessation
- 2005-05-03 TW TW094114245A patent/TW200536541A/zh unknown
- 2005-05-03 PE PE2005000493A patent/PE20060306A1/es not_active Application Discontinuation
- 2005-05-03 GT GT200500101A patent/GT200500101A/es unknown
- 2005-05-04 SV SV2005002102A patent/SV2005002102A/es not_active Application Discontinuation
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2006
- 2006-10-06 ZA ZA200608393A patent/ZA200608393B/en unknown
- 2006-10-17 IL IL178676A patent/IL178676A0/en unknown
- 2006-11-01 EC EC2006006968A patent/ECSP066968A/es unknown
- 2006-11-03 MA MA29436A patent/MA28571B1/fr unknown
- 2006-11-03 TN TNP2006000358A patent/TNSN06358A1/fr unknown
- 2006-11-03 CR CR8730A patent/CR8730A/es not_active Application Discontinuation
- 2006-12-04 NO NO20065578A patent/NO20065578L/no not_active Application Discontinuation
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2009
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